At SAGE Labs (USA), two first transgenic rat models of autism spectrum disorder (ASD) (syndromic and nonsyndromic) were engineered using ZFNs to knock-out the gene of Fragile X mental retardation protein (FMRP) and Neuroligin3 gene (NLGN3).
Fmr1 and Nlgn3 knockout rats: Novel tools for investigating autism spectrum disorders.
C57BL/ 6J mice, a strain commonly used in addiction studies due to their high levels of self-administration of most drugs of abuse, have lower levels of Nrxn2[beta] and Nlgn3 expression in the substantia nigra and increased expression of Nlgn1 in the subthalamic nucleus compared to non-drug-preferring mice .
Cell adhesion molecule Abbreviation Neural cell adhesion molecule NCAM Polysialated neural cell adhesion molecule PSA-NCAM Neuronal cell adhesion molecule NRCAM Immunoglobulin super family IGSF Synaptic cell adhesion molecule SYNCAM Intercellular adhesion molecule 5 ICAM5 Cadherin 13 CDH13 Neurexin 3 NRXN3 Neurexin 2[beta] NRXN2[beta] Neuroligin 3 NLGN3 Neuroligan 1 NLGN1 Neurexin 3[beta] NRXN3[beta] Protein tyrosine phosphatase receptor D PTPRD Protein tyrosine phosphatase receptor B PTPRB CUB and Sushi multiple domains 1 CSMD1 Protein tyrosine phosphatase receptor Z 1 PTPRZ1 Table 2: Gene expression changes after repeated cocaine treatment.
NLG R451C mice are genetically engineered to contain a rare missense mutation of the Nlgn3
gene, a mutation also found in some individuals with ASDs.
Mutations of the x-linked genes encoding neurologins NLGN3
and NLGN4 are associated with autism.
So extending the assumption of X chromosome evolution from autosome we can assume that paralog of X-linked genes must be on autosome and should be involved in the same disorder; like ARHGEF6 (X chromosome) has its paralog ARHGEF3 and ARHGEF4 on autosome; similarly NLGN3
, NLGN4 on X -chromosome has paralog NLGN1 and NLGN2 on autosome.
El gen IL13RA3 esta localizado en el cromosoma Xq13.1-q28, donde se han descrito ligamiento con LOD score mayor a 2 y alteraciones citogeneticas (60, 61); por lo que han sido postulados otros genes candidato como los genes de las neuroliguinas 3 y 4 (NLGN3 o Neuroligin 3) (25).
Paris Autism Research International Sibpair Study: Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.
Third, neuronal cell adhesion molecules Neuroligin (Nlgn) and Neurexin (Nrxn) are essential for synaptic structure and function in the synaptic cleft and Nlgn3
and Nrxn1 have been associated with autism .
NLGN1 and NLGN3
have increased surface membrane levels upon chemically induced LTP and decreased levels after LTD as a result of being dynamically exchanged at the postsynaptic membrane through active cytoskeleton transport .
Butler, "Novel splice isoforms for NLGN3
and NLGN4 with possible implications in autism," Journal of medical genetics, vol.